Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)

Abstract Background Oxytocin administration is increasingly considered a novel therapeutic support option for alleviating psychological distress in stress-related neuropsychiatric conditions, including anxiety disorders and depression. However, oxytocin as a stand-alone treatment may fail to consist...

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Main Authors: E. van Weert, HJ. De Vuyst, K. Van der Gucht, E. Debbaut, J. Steyaert, K. Alaerts
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07077-8
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author E. van Weert
HJ. De Vuyst
K. Van der Gucht
E. Debbaut
J. Steyaert
K. Alaerts
author_facet E. van Weert
HJ. De Vuyst
K. Van der Gucht
E. Debbaut
J. Steyaert
K. Alaerts
author_sort E. van Weert
collection DOAJ
description Abstract Background Oxytocin administration is increasingly considered a novel therapeutic support option for alleviating psychological distress in stress-related neuropsychiatric conditions, including anxiety disorders and depression. However, oxytocin as a stand-alone treatment may fail to consistently target the relevant central autonomic circuitry without a complementary supportive therapeutic context that similarly stimulates stress-regulatory states and behaviors. Recent findings suggest that the neurophysiological mechanisms underlying stress regulation induced by mindfulness may rely on an activation of the endogenous oxytocinergic system. Accordingly, combining oxytocin with a mindfulness-based training program may enhance efficacy compared to each intervention alone. Methods A randomized, double-blind, placebo-controlled clinical trial will be conducted in 120 adults with heightened stress complaints, randomly assigned to one of the following four treatment arms (n = 30 per group): (1) oxytocin + mindfulness, (2) mindfulness + placebo, (3) oxytocin, and (4) placebo (control). The oxytocin or placebo nasal spray will be administered four times a week in the morning before each mindfulness session for six weeks, followed by a six-week post-treatment follow-up session. Primary endpoints include self-reported behavioral measures of stress, depression, and anxiety. Secondary endpoints include self-reported behavioral measures of mood, mindfulness skills, quality of life, sleep quality, and negative thinking. Exploratory measures include (i) electroencephalography (EEG), electrocardiography (ECG), skin conductance, and respiration, measured during rest, meditation, stress induction, and stress recovery; (ii) intervention-induced changes in biological samples, including hormonal levels of oxytocin and cortisol and DNA methylation of the oxytocin receptor gene (OXTR); and (iii) stress reactivity in daily life, assessed through experience sampling and heart rate/sleep monitoring. All outcome measures will be assessed at baseline (T0), immediately post-intervention (T1), and at six-week follow-up (T2). Discussion These findings could provide valuable insights into how combining oxytocin and mindfulness-based interventions might enhance stress regulation, particularly in populations with impaired oxytocinergic function. Trial registration This trial was registered in the EU Clinical Trials Register (EU CT 2024–513482-39–00) on 18 March 2025.
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spelling doaj-art-c2acdca4e1dc4b5a80b00c15fec0a7f22025-08-20T03:45:31ZengBMCBMC Psychiatry1471-244X2025-07-0125111210.1186/s12888-025-07077-8Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)E. van Weert0HJ. De Vuyst1K. Van der Gucht2E. Debbaut3J. Steyaert4K. Alaerts5Neuromodulation Laboratory, Department of Rehabilitation Sciences, KU LeuvenNeuromodulation Laboratory, Department of Rehabilitation Sciences, KU LeuvenFaculty of Psychology and Educational Sciences, Leuven Mindfulness Consortium, KU LeuvenLeuven Autism Research (LAuRes), KU LeuvenLeuven Autism Research (LAuRes), KU LeuvenNeuromodulation Laboratory, Department of Rehabilitation Sciences, KU LeuvenAbstract Background Oxytocin administration is increasingly considered a novel therapeutic support option for alleviating psychological distress in stress-related neuropsychiatric conditions, including anxiety disorders and depression. However, oxytocin as a stand-alone treatment may fail to consistently target the relevant central autonomic circuitry without a complementary supportive therapeutic context that similarly stimulates stress-regulatory states and behaviors. Recent findings suggest that the neurophysiological mechanisms underlying stress regulation induced by mindfulness may rely on an activation of the endogenous oxytocinergic system. Accordingly, combining oxytocin with a mindfulness-based training program may enhance efficacy compared to each intervention alone. Methods A randomized, double-blind, placebo-controlled clinical trial will be conducted in 120 adults with heightened stress complaints, randomly assigned to one of the following four treatment arms (n = 30 per group): (1) oxytocin + mindfulness, (2) mindfulness + placebo, (3) oxytocin, and (4) placebo (control). The oxytocin or placebo nasal spray will be administered four times a week in the morning before each mindfulness session for six weeks, followed by a six-week post-treatment follow-up session. Primary endpoints include self-reported behavioral measures of stress, depression, and anxiety. Secondary endpoints include self-reported behavioral measures of mood, mindfulness skills, quality of life, sleep quality, and negative thinking. Exploratory measures include (i) electroencephalography (EEG), electrocardiography (ECG), skin conductance, and respiration, measured during rest, meditation, stress induction, and stress recovery; (ii) intervention-induced changes in biological samples, including hormonal levels of oxytocin and cortisol and DNA methylation of the oxytocin receptor gene (OXTR); and (iii) stress reactivity in daily life, assessed through experience sampling and heart rate/sleep monitoring. All outcome measures will be assessed at baseline (T0), immediately post-intervention (T1), and at six-week follow-up (T2). Discussion These findings could provide valuable insights into how combining oxytocin and mindfulness-based interventions might enhance stress regulation, particularly in populations with impaired oxytocinergic function. Trial registration This trial was registered in the EU Clinical Trials Register (EU CT 2024–513482-39–00) on 18 March 2025.https://doi.org/10.1186/s12888-025-07077-8OxytocinYoung adultsMindfulnessStress regulationClinical trial
spellingShingle E. van Weert
HJ. De Vuyst
K. Van der Gucht
E. Debbaut
J. Steyaert
K. Alaerts
Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
BMC Psychiatry
Oxytocin
Young adults
Mindfulness
Stress regulation
Clinical trial
title Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
title_full Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
title_fullStr Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
title_full_unstemmed Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
title_short Exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress: study protocol for a double-blind, randomized, placebo-controlled trial (MOX-MIND)
title_sort exploring the mechanistic link between the oxytocinergic system and mindfulness training in adults with heightened stress study protocol for a double blind randomized placebo controlled trial mox mind
topic Oxytocin
Young adults
Mindfulness
Stress regulation
Clinical trial
url https://doi.org/10.1186/s12888-025-07077-8
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